The goal of this study is to assay the role that two modulators of microtubule dynamics, Mitotic centromere-associated Kinesin (MCAK) and 0p18/stathmin (stathmin) play in the development of cancer. These proteins are elevated in aggressive breast cancer tumors and changes in the levels and activity of these proteins have been correlated with alterations in chromosome number and cell motility and invasiveness. In addition to our previously discovered C-terminal regulation, we have uncovered another major regulatory mechanism to control microtubule dynamics through MCAK activity. Phosphorylation of conserved serine residue in the neck and N-terminus of MCAK by Aurora B kinase inhibits its activity. It is likely that phosphorylatin and dephosphorylatin controls MCAK's activity during mitosis and also, via other kinases, during interphase. We have also identified two other Kin I kinesisns which regulate microtubule dynamics in cultured cells and are likely to be regulated by kinases and phosphatases. These regulatory kinases also control stathmin activity in cells. Regulation of these proteins via cascades of kinase and phosphatase activities opens up a major new area for the application of therapeutics to control microtubule dynamics and augment existing cancer therapies that target microtubules.